Endometrial carcinoma is the most common gynecologic cancer in the United States, with >7400 deaths per year and a death rate that has doubled since 1985. The increase in mortality rates in women with endometrial cancer is related to an increase in patients with advanced-stage cancers and a larger proportion of high-risk histologic conditions. Current diagnostic approaches rely on endometrial sampling of macroscopic disease that is driven by the presence of symptoms and signs that include vaginal bleeding and metrorrhagia. The key to an improved progression-free survival and overall survival is the early diagnosis of microinvasive disease, which is curable more readily with the use of either hormonal or surgical treatment modalities.
To date, there are no reliable serum biomarkers in clinical use for the detection of endometrioid, clear cell, or papillary serous adenocarcinoma of the endometrium. Serum cancer antigen 125 (CA125) is a high molecular weight glycoprotein and serum CA125 levels ≦35 units/mL are accepted as normal. CA125 is currently only relatively accurate in the detection of late stage ovarian cancer (papillary serous histologic subtype), is not used for the detection of endometrial cancer.
Although novel proteomic-based approaches have been used successfully to detect and diagnose a number of different types of cancers, none have been reported for endometrial cancer. We analyzed protein profiles using surface enhanced laser desorption and ionization time-of-flight mass spectroscopy and identified 3 serum proteins (namely, apolipoprotein-1 [ApoA-I], prealbumin [transthyretin or TTR], and transferrin [TF]) for the early detection of ovarian cancer. We have further discovered that the 3 markers that were described for ovarian cancer can be used in the diagnosis of early- or late-stage endometrial cancer. The invention therefore addresses the need for improved tools to permit the early detection and prognosis of cancer, particularly endometrial and ovarian cancers. There also remains a need for targets useful in the detection and treatment of cancer.